SLC24A5 rs11265263: What Your Genotype Means
rs11265263 is a single nucleotide polymorphism located in the SLC24A5 gene on chromosome 15. It functions primarily as a synonymous tag variant in strong linkage disequilibrium with the major European skin-lightening allele Ala111Thr (rs1426654). Because of this close genetic linkage, rs11265263 reflects population-level differences in melanogenesis and melanin index variation rather than causing functional changes itself.
What each genotype means
Typical ancestral pigmentation
This genotype represents the ancestral state of the SLC24A5 region. It is strongly associated with higher levels of melanin production in populations where this variant is the primary form, though it is not a diagnostic indicator of specific skin tone.
This is the most common genotype in African and East Asian populations, while it is rare in European populations.
Intermediate pigmentation association
Carrying one copy of the A allele suggests a genetic background that may influence melanogenesis differently than the ancestral state. This variant is in strong linkage disequilibrium with the primary skin-lightening coding variant Ala111Thr, and its effect on your specific phenotype is part of a complex, polygenic trait.
This heterozygous genotype is found at varying frequencies in admixed populations and is less common in populations where either the A or C allele is near fixation.
Associated with lighter pigmentation
This genotype is in strong linkage disequilibrium with the primary European skin-lightening variant Ala111Thr in the SLC24A5 gene. It is statistically associated with reduced melanin content in the skin, though it is only one of many genetic factors that contribute to human pigmentation traits.
This is the predominant genotype in European populations and is also found in significant frequencies in South Asian populations.
Genomic Location and Variant Classification
The single nucleotide polymorphism rs11265263 is situated within the SLC24A5 gene locus on the human genome. Rather than directly altering protein structure or amino acid sequences, rs11265263 is classified as a synonymous or non-coding tag marker. In human genomics, tag SNPs are variants that travel together with functional changes across generations on shared ancestral haplotypes. For rs11265263, its biological relevance is derived from its strong linkage disequilibrium with rs1426654, the missense mutation that encodes the Ala111Thr substitution. Genotyping arrays frequently include rs11265263 because it reliably tracks this surrounding haplotype, enabling researchers to reconstruct human demographic history and pigmentation genetics without directly sequencing every base pair.
Biological Function of SLC24A5 and Melanogenesis
The SLC24A5 gene provides instructions for producing sodium/potassium/calcium exchanger 5 (NCKX5), a transport protein situated in the membranes of intracellular organelles, specifically melanosomes. Melanosomes are specialized cellular compartments within melanocytes responsible for synthesizing, storing, and distributing melanin pigments. NCKX5 regulates calcium ion homeostasis across melanosomal membranes, a crucial biophysical process required for the enzymatic activity of tyrosinase and the overall maturation of melanosomes. Changes in this cation exchange activity influence whether melanosomes produce denser, darker eumelanin or lighter pigment phenotypes. The canonical functional variant in SLC24A5, rs1426654, substantially modulates melanosome size and pigment density, establishing the gene as a central player in normal human phenotypic diversity.
Research Associations and Evidence Strength
Evidence directly attributing physiological effects to rs11265263 is considered limited because it is not the causal driver of melanogenesis. Instead, published genome-wide association studies and population genetic surveys demonstrate that rs11265263 is inherited alongside the causal Ala111Thr variant. In European and West Eurasian ancestral cohorts, the derived allele is nearly fixed as a result of past positive selection for lighter skin pigmentation. Linkage disequilibrium studies, such as those cataloged in dbSNP and PubMed, show that having the C allele at rs11265263 reliably indicates co-inheritance of the light-pigmentation haplotype. However, researchers emphasize that skin color is an extensively polygenic trait influenced by dozens of genes, including SLC45A2, TYR, and MC1R, meaning single tag markers only capture a fraction of complex phenotypic variation.
What You Can and Cannot Conclude
Understanding your rs11265263 genotype offers insight into human population genetics, ancestry-informative markers, and historical natural selection, but it has important limitations. A genotype at this single marker cannot definitively predict your precise skin shade, tanning ability, or personal health status. Polygenic traits arise from the coordinated activity of hundreds of genetic variants interacting with ultraviolet radiation and geographic environments. Furthermore, because rs11265263 is a tag SNP, its correlation with specific physical traits depends heavily on individual ancestral background. Individuals should avoid treating direct-to-consumer genetic readouts as diagnostic health metrics, and anyone evaluating sun exposure risks or skin health should consult certified dermatologists rather than interpreting isolated genetic markers.
How common is this variant?
The C allele frequency is approximately 0.98 in individuals of European descent, while it drops to approximately 0.05 in indigenous African populations. Intermediate frequencies are commonly observed across South Asian and admixed populations.
Frequently asked questions
What does rs11265263 tell me about my skin color?
rs11265263 is a tag variant that reflects which version of the SLC24A5 gene region you inherited. While the C allele statistically tracks with lighter skin pigmentation in European populations, skin tone is influenced by many genes, so this marker alone cannot accurately predict your personal appearance.
Does having a specific rs11265263 genotype cause health problems?
No, rs11265263 is considered a benign trait marker associated with normal variation in pigmentation and ancestry. It is not classified as a pathogenic mutation and does not directly cause disease or skin disorders.
How does rs11265263 differ from rs1426654?
rs1426654 is the functional missense mutation that directly changes an amino acid (Ala111Thr) in the SLC24A5 protein, whereas rs11265263 is a synonymous tag variant. Because they sit near each other on chromosome 15, they are inherited together in strong linkage disequilibrium.
Why is the C allele so common in Europeans compared to other populations?
Evolutionary biologists believe that positive natural selection favored the derived SLC24A5 haplotype in northern latitudes over the past tens of thousands of years. This selective pressure likely facilitated cutaneous vitamin D synthesis in environments with lower sunlight levels.
Sources & further reading
Educational information only, last refreshed 9/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This SNP is a primary determinant of human skin pigmentation variation globally.
Regulatory variant in the SLC24A5 locus associated with skin pigmentation variation.
Lesser-studied regulatory variant linked to human skin pigmentation gradations and melanogenesis.
Coding variant in SLC24A5 strongly associated with skin pigmentation and melanin distribution.
Non-coding regulatory SNP in strong linkage disequilibrium with Ala111Thr, regulating melanocytic gene expression and skin lightness traits.
A coding variant (Ala111Thr) in SLC24A5 that is a major determinant of human skin pigmentation differences between European and African populations.